System and method for cortical mapping without direct cortical stimulation and with little required communication

ABSTRACT

An apparatus for cortical mapping and method for using same are disclosed. The apparatus comprises a ECoG electrodes array, a stimulation pad, a neural interface processor, and a computing device for mapping eloquent cortical regions of a subject&#39;s brain without using exogenous stimulation and with high resolution.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.15/147,843, filed under the same title on May 5, 2016, and claiming thebenefit of U.S. Provisional Application Ser. No. 62/162,431 filed on May15, 2015, the entirety of both applications being incorporated herein byreference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

N/A

BACKGROUND

Approximately 65 million individuals worldwide are living with epilepsy.The first and most common form of relief relies on anti-epileptic drugs.However, one-fourth to one-third of the cases do not become seizure-freefrom drug therapy alone. In these situations, surgery may be an optionif a single, localizable focus can be identified and safely removed.

To obtain a broad sense of the origins and types of seizures, neuralactivity is first monitored using an electroencephalography (EEG) systemthrough scalp recordings of brain activity (Phase I). If the seizuresappear to be potentially focal and unilateral, surgically implantedelectrocorticographic (ECoG) electrodes on the cortical surface, ordepth electrodes for deep foci, are used to monitor cortical activityduring seizures and further define the epileptic foci (Phase II). Thedecision for surgical resection or intervention depends on the data fromthis invasive monitoring strategy that delineates the epileptogenic zoneto ensure that resection of the seizure foci will not significantlyimpact neurological functions. During Phase II monitoring, in additionto seizure localization, several procedures are used to define areas ofeloquent cortex, which is used to describe areas of cortex that—ifremoved—will result in loss of sensory processing or linguistic ability,minor paralysis, or paralysis, and attempt to estimate the cognitivefunctions possibly affected by respective surgery.

Electrical Cortical Stimulation (ECS) is considered the gold standardfor sensorimotor functional delineation of eloquent tissue in the brain.In contrast to continuous monitoring where the electrical current fromthe brain is passively recorded, electrical current is passed betweenneighboring electrodes to evoke sensory or motor manifestations.Typically during ECS, 50 Hz square pulse trains are applied lasting twoto five seconds. The stimulation current is gradually increased up to 10mA until a sensory, a motor, or an after-discharge response is elicited.

A bottom-up approach can also be used for the mapping where peripheralnerves are electrically stimulated and evoked responses in the corticalsignals are visually observed. However those two techniques havelimitations. The somatic response is subjective and interpretative basedon the subject's response and direct observation by the tester. Corticalstimulation does not always elicit motor responses in children under tenyears of age. For sensory areas, it is often difficult to interpretevoked stimuli. In children, particularly those who are too young ornon-verbal due to cognitive dysfunction, interpretation of sensation canbe very difficult. Additionally, after-discharges, an unwantedconsequence of ECS stimulation, are frequent, and can lead to seizures.

Therefore, it would be desirable to have a system and method forcortical mapping that does not use electrical stimulation but producesresolution comparable with that with electrical stimulation, or requiredetailed or any communication with the patients during the mapping.

SUMMARY

The present disclosure overcomes the aforementioned drawbacks byproviding a system and method that delivers vibration to the skin ratherthan electrical stimulation to the brain. The vibrations serve asstimulation or cues for movement. For somatosensory cortex mapping,little communication with the subject is required. So is motor cortexmapping if the subject receives movement instructions before the mappingprocedures start.

The Applicant's disclosure relates generally to an apparatus for mappingsomatosensory and motor cortical regions of a brain of a subject who isundergoing electrocorticoencephalographic (ECoG) recording. In certainembodiments, the apparatus comprises a computing device, a stimulationpad interconnected to said computing device, wherein said stimulationpad is configured to be brought into physical contact with a selectedregion of the subject's skin; a neural interface processorinterconnected to said computing device; and an ECoG electrodes array tobe implanted on a surface of the subject's brain, wherein said ECogelectrode array is in communication with the neural interface processor.

Additionally, the Applicant's disclosure relates generally to a methodfor mapping somatosensory and motor cortical regions of a brain of asubject who is undergoing electrocorticoencephalographic (ECoG)recording. In certain embodiments, the method comprises the steps ofproviding an apparatus comprising a computing device, a stimulation padinterconnected to said computing device, a neural interface processorinterconnected to said computing device; implanting a ECoG electrodesarray on a surface of the subject's brain; contacting said stimulationpad with a selected region of the patient's skin; producing during afirst period of time stimulation of said selected region; recording bysaid neural interface processor a plurality of cortical signalsoriginating in said subject's brain; based upon said plurality ofcortical signals, mapping eloquent cortical regions of the subject'sbrain; generating a 3-D mapping in combination with a plurality oflandmark locations of said subject's brain using one or more medicalimaging techniques; forming a composite image by overlaying an image ofsaid ECoG electrode array onto said 3-D mapping with said landmarklocations; and comparing the mapped eloquent cortical regions to saidcomposite image to reduce a risk of causing brain injury during asurgical remediation of epileptic seizures.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram of an example system implemented for somatosensorycortex mapping according to the present application.

FIG. 2 is a flowchart of an example method of somatosensory cortexmapping implemented according to the present application.

FIGS. 3A and 3B illustrate Temporal and Spectrotemporal response tovibrotactile stimuli on Sub1. FIGS. 3A and 3B represent the averageresponse to vibrotactile stimulation under four experimental conditions(CLs: Contralateral sensory, CLsm: Contralateral sensorimotor, ILs:Ipsilateral Sensory, and ILsm: Ipsilateral Sensorimotor). The top ofeach of FIGS. 3A and 3B represents the average evoked response; thebottom part shows its average time-frequency representation over thefive fingers (ERS in red, ERD in blue). Traces are color coded perstimulated finger as shown in the bottom-left sketch.

FIG. 4 is a diagrammatic plot illustrating elicited response (80-120 ms)in the temporal (Left-top), and spectrotemporal (Left-bottom) domains tovibratory contralateral stimulation of the five fingers, and clinicalelectrical mapping (Right), in which labels represent clinical mappingresults (H: Hand, F: Fingers, numbers represent individual digits, s/mrespectively sensory and motor).

FIGS. 5A-E are plots illustrating time-frequency evolution of electrodeswith significant Mid Gamma clusters, and associated Event RelatedPotentials (black traces), averaged across subjects for the thumb,index, middle, ring, and small fingers, respectively.

FIG. 6 is a diagrammatic plot illustrating clinical electrical mappingvs. vibrotactile sensory mapping of the contralateral fingers. Clinicalmapping results are indicated with numbers and letters on the corticalsurface (H: Hand, F: Fingers, 1-2-3-4-5 individual digits, s/msensory/motor). Superimposed on those cortical maps, the colored spheres(as in FIG. 3) represent one result from the vibrotactile mapping. Starsindicate electrodes with a late lateral response described below.

FIGS. 7A-D are plots illustrating late lateral response averaged overfour subjects.

DETAILED DESCRIPTION

This invention is described in preferred embodiments in the followingdescription with reference to the Figures, in which like numbersrepresent the same or similar elements. Reference throughout thisspecification to “one embodiment,” “an embodiment,” or similar languagemeans that a particular feature, structure, or characteristic describedin connection with the embodiment is included in at least one embodimentof the present invention. Thus, appearances of the phrases “in oneembodiment,” “in an embodiment,” and similar language throughout thisspecification may, but do not necessarily, all refer to the sameembodiment.

The described features, structures, or characteristics of the inventionmay be combined in any suitable manner in one or more embodiments. Inthe following description, numerous specific details are recited toprovide a thorough understanding of embodiments of the invention. Oneskilled in the relevant art will recognize, however, that the inventionmay be practiced without one or more of the specific details, or withother methods, components, materials, and so forth. In other instances,well-known structures, materials, or operations are not shown ordescribed in detail to avoid obscuring aspects of the invention.

The system and method disclosed herein can map somatosensory and motorcortexes without direct cortical stimulation or depending on biasedinterpretation by the subject. Little communication with the subject isrequired, so the system and method can produce maps even of unresponsivesubjects.

Vibratory stimuli are relayed by the lemniscal pathway from thecutaneous mechanoreceptors to the somatosensory cortical areas.Epicritic inputs from the lemniscal system are transmitted from theventroposteriolateral nucleus of the thalamus to several cortical areas.By mapping the cortical areas in response to the vibratory stimuli,physicians intend to avoid those cortical areas and preserve thefunctions of those areas when resecting cortical areas responsible forepileptic seizures.

Finger representation in the contralateral primary sensory cortex (SI)covers about a 10-20 mm long cortical strip, following a latero-medialdistribution, from the thumb to the small finger with a limited amountof overlap and notable inter-individual variability. As describedherein, “about” means a 10% difference in measurement. The secondarysensory cortex (SII) does not seem to follow a topological organizationof the fingers or show a strong spatial overlap, and may be involved inbimanual tasks.

Referring now to FIG. 1, an embodiment of an apparatus 100 for mappingsomatosensory and motor cortical regions of a brain of a patient who isundergoing electrocorticoencephalographic (ECoG) recording to locateareas of eloquent cortex and reduce a risk of causing permanent braininjury during surgical remediation of seizures is shown here. Thisembodiment should not be construed as limiting on the invention. Asubject's fingers can be placed in a stimulation pad 102. In certainembodiments, the stimulation pad 102 further comprises a plurality ofvibration motors 102 a and a plurality of force sensitive resistors 102b. In one embodiment, the plurality of vibration motors comprises 5about 10 millimeter (mm) shaftless vibration motors. In anotherembodiment, the plurality of force sensitive resistors 102 b comprises 50.5 inch long force sensitive resistors. The vibration motor produces asmall buzzing sensation when pressed to the skin and activated.Vibratory stimulation at ˜60 Hz is known to activate a variety ofperipheral receptors and thus produce a robust neural response that canbe measured as changes in the ECoG signals. Vibrations delivered by thestimulation pad 102 can also serve as cues for movement. For thispurpose, the vibrator may comprise a thin-film pressure transducermounted in container that can be manufactured by rapid prototyping. Sowhen a subject's finger is placed in the device, it can be vibrated formapping the hand area of somatosensory cortex and monitored for pressureapplied by the subject's finger to map the hand area of motor cortex.

Each of the 5 shaftless vibration motors and each of the 5 forcesensitive resistors are encased in a customized finger placeholder thatcan be manufactured using rapid prototyping. Further, each of these 5finger placeholders is placed on a slotted foam stimulation pad 102. Incertain embodiments, the stimulation pad 102 is able to be adjusted insize to accommodate smaller hands for younger patients. Moreover,vibration interference between fingers is able to be reduced in thestimulation pad 102.

A neural interface processor 104 conducts signals to the stimulation pad102 with respect to the stimulation of vibration, the frequency ofvibration, the time period of the vibration, the time period of thevibration interference, and the synchronizing pressure values from thefingers to the cortical signals. Furthermore, the neural interfaceprocessor 104 measures delays and rising time of the motors forcorrection during data analysis. In some embodiments, the neuralinterface processor comprises a microcontroller, which is able to beprogrammed and can communicate with a computing device 106. In someembodiments, the computing device 106 is a computer with a customizedprogram encoded. In addition, the neural interface processor 104comprises an ECoG-recording device 108, which is able to collect digitaland analog signals indicating the beginning of a vibratory stimulus ordetection of a change in the pressure on the pressure sensor. Thisenables a quick alignment of the ECoG data with behavioral and stimulusevents at the periphery.

In certain embodiments, the vibrations stimulate the fingers and mayalso serve as cues for the subject to move the fingers. Neuralactivities in response to the stimulation or the cues are recorded withan ECoG electrodes array 110. The ECoG electrodes array 110 is implanteddirectly on the brain that is exposed by a surgical opening 114.Compared with EEG recordings, ECoG electrodes lie on the surface of thebrain, providing increased spatial resolution and higher signal to noiseratio. Array locations can be selected from the observations duringPhase I monitoring and no additional implants are required. To map thesomatosensory and the motor cortexes, the array covers the region ofprimary motor cortex 108 and primary sensory cortex 112. The ECoGsignals are detected and recorded with a ECoG-recording device 108 andthen sent to computing device 106. The computing device 106 processesthe signals to determine neural activities in response to thestimulation or cues, determine specific electrodes in the ECoGelectrodes array 110 that have detected the neural activities, anddisplays the locations of the specific electrodes overlaid on brainimages acquired with a medical imaging modality. Such a modality can becomputed tomography (CT) or magnetic resonance imaging (MRI).

Referring to FIG. 2, a flowchart 200 of an example method implementedaccording to the present application is provided. In step 202,vibrations are provided to stimulate digits of a subject or as cues formovement of the digits. In step 204, ECoG signals of the brain inresponse to the stimulation or the cues are detected and recorded by theneural interface processor 104. The recorded ECoG signals aretransferred to the computing device 106 for further calculation andstatistical analysis. In step 206, the ECoG signals are analyzed todetermine neural activities evoked by the stimulation or the cues. Instep 208, brain locations having those evoked neural activities aredetermined and mapped. In step 210, for better visualization, thelocations having the neural activities are overlaid on images acquiredwith a medical imaging modality, such as CT or MRI. These applicationsoften include landmark-based image registration, segmentation of brainstructures, prospective subject positioning in longitudinal imaging.Landmarks are specific structures with distinguishable morphologicalcharacteristics. The most basic method for locating anatomical landmarkson MRI is manual placement by a trained operator.

The ECoG signals are processed to reduce noise and prepare for analysis.One source of noise is the fluctuation in the background corticalrecordings. Background cortical recordings show a significant amount ofnatural fluctuations due to variations in arousal, focus, oruncontrolled external stimuli during the course of the mapping, all ofwhich can affect the mapping outcome. To minimize this effect, as manytrials as possible can be recorded for each condition and for allstatistical tests; baseline correction is performed from 150 ms to 10 msbefore stimulation. The computing device can also determine whichelectrodes have responses associated with the tactile stimulation or themovement by rapidly scanning activities across the entire set ofelectrodes. It can also register the physiological results from the ECoGsignals with anatomical images obtained by MRI and CT.

Referring to FIGS. 3A-B, in certain embodiments, a subject performs twotasks: a sensory only (s) and a sensorimotor (sm) task performedcontralaterally (CL) or ipsilaterally (IL) to the recording grids ofinterest, leading to four experimental conditions: CLs, CLsm, ILs, andILsm. In the sensory only task, while patients sat comfortably in theirhospital bed, their fingers were placed on the stimulation pad 102designed to individually stimulate the fingers. One hand at a time, thepatients' fingers were randomly vibrated for a period ranging from 100ms to 500 ms, with an inter-stimulation interval ranging from is to 1.4s. In the sensorimotor task, the stimulation remained the same, but thepatients were instructed to attend to the stimulus by pressing thecorresponding finger on the stimulation pad 102. The time allowed formotor response was set to 4 s, with an inter-trial interval of 1.5 s.Each set consisted of 50 trials (ten per finger), after which hands wereswitched. Up to 30 sets over a period of several days according to thepatients' physical and mental status are recorded.

In certain embodiments, the signals are analyzed in the time domain.Time domain analysis typically focuses on evoked potentials, averagingcortical responses over large numbers of trials. This procedure enhancestime locked components and reduces the impact of non-related activity.Somatosensory Evoked Potentials (SEPs) can be elicited by stimulatingperipheral nerve fibers.

In other embodiments, the ECoG signals can also be analyzed in thetime-frequency domain. Time-frequency domain analysis expands theanalysis of evoked responses to changes in oscillatory activity inducedby stimulation. Evoked Response Synchronization (ERS) and EvokedResponse Desynchronization (ERD) correspond respectively to an increaseor decrease of the power of oscillations in a given band. ERS may emergeas the result of a surge of concurrent activity in a network while ERDmay arise as the result of a decreased correlation. Smaller functionalnetworks may exhibit higher ERS frequencies than larger areas.

Referring again to FIGS. 3A-B, the response of the postcentral-medialelectrode 310 to contralateral sensory stimulation (FIG. 3A) begins witha N40 peaking across fingers at an average at 38 ms, followed by P100(108 ms), N140 (138 ms), and P200 (186 ms), before returning to baselinelevels. The frequency domain response shows a wide broadband increase inthe high frequency range coinciding with the first peak, followed by alow frequency rebound. Similar responses for this electrode can be seenin the contralateral sensorimotor task, with larger amplitudes. Theresponse of the precentral-medial electrode 320 (FIG. 3B) presents aN100 followed by a high frequency increase in both contralateral tasks,as well as a delayed high frequency increase in the ILsm task.

Referring to FIG. 4, across subjects, the time-frequency domain showedmore spatially localized responses, as shown for Sub1 in the left panel.For this subject, both domains presented the accepted precentrallatero-medial somatotopic distribution. However, in the frequencydomain, the elicited response is more demarcated from the background andmore spatially focused. For this subject, clinical mapping (right panel)located broad fingers/hand regions, but in some cases, postcentralstimulation lead to motor responses.

A cluster-based nonparametric permutation test can be used to addressnon-Gaussian distributions of the ECoG signals and multiple comparisonsissues. A multiple comparison problem arises when a large number ofstatistical tests are simultaneously performed. It can be minimized withthe Bonferonni correction. The nonparametric permutation test takesadvantage of the significant correlation between adjacent electrodes tolower the family-wise error rate in the Bonferonni correction and at thesame time increase sensitivity of the test. This method results inclusters of adjacent time-domain or time-frequency-domain samples,depicting significant activation originating from the precentral cortexor above the central sulcus. Cluster detection can be applied on thefull band spectrum, in addition to a per-band basis. This can lead tocluster localization in the time-frequency-space domain instead oftime-band-space domain and may provide information on the spectralevolution of elicited activity.

Across all subjects, conditions and stimulated fingers, clustering inthe spectrotemporal domain led to 151 significant (p≤0.05) clustersappearing within 240 milliseconds after stimulation (Table 2); 40.4% ofwhich started as contralateral ERS above 65 Hz, while 17.9% correspondedto a contralateral ERD below 30 Hz. The smaller number seen in CLsm ascompared to CLs seems to originate from a higher residual pre-stimulusactivity, preventing some clusters from exhibiting significance at thislevel. Significant clusters emerged earlier in the most active ERD band(MidG: 118.1 ms) than in the most active ERD band (Beta: 143.4 ms).

TABLE 2 Number of significant ERS/ERD clusters across conditions andsubjects (p ≤ 0.05) Alpha Beta LowG MidG HigG CLs 2/8  0/13 0/2 29/111/1 CLsm 3/1 1/5 1/1 14/1  7/0 ILs 4/2 3/2 3/1  4/3 10/2 ILsm 4/1 1/11/2  2/2  1/1

Referring to FIGS. 5A-E, in certain embodiments, due to the latencyjitter often observed in the time domain and the inherent highbackground noise in our patient population, the study is focused on inthe time-frequency domain, and specifically the Mid-Gamma event relatedsynchronization. Across subjects, the electrodes presenting significantclusters in the MidG band presented an early ERS (areas shaded bydashes) followed by a late ERD (areas shaded by circles).

Referring to FIG. 6, in order to evaluate Mid-Gamma activations for eachdigit, the tridimensional location of electrodes belonging to the mostsignificant cluster are weighted by their absolute power and representedby the colored spheres on the cortical models. Across subjects, thevibrotactile task led to clustered localizations of the contralateralfingers, spanning less than 20 mm. In certain embodiments, the estimateddigital areas were located posteriorly or above the central sulcus, inagreement with anatomical expectations. In comparison, electricalstimulation leads to broad representations of the hand/digits and seldomlocated sensory areas.

Referring to FIGS. 7A-D, in certain embodiments, some subjects underwenta sensorimotor task requiring a finger press in response to thevibrotactile stimuli. For those subjects, an additional broadbandresponse was detected. These late responses, localized in the electrodesmarked in FIG. 6 with a yellow star, were stronger under thesensorimotor task than in the sensory only task. Their near-Sylvianlocation and the delay to the initial response are relatively consistentwith the secondary somatosensory areas and their delayed activationseems to imply a secondary processing or motor planning. The relation ofthe frequency response with respect to two late negative ERP peaks isalso observed.

The vibrators allow single digit stimulation and can elicit reliableevent-related potential (ERP), ERD and ERS responses, independently ofsubject wakefulness and mental capacity. Evoked response potentials inthe time domain are often degraded by interictal background noise andjitter, while the frequency representations show more consistency. Theclustering-based statistical approach—taking into account adjacencyrelationships in time, frequency, and space—can reliably detectsignificant ERS/ERD clusters in relevant cortical areas within theMid-Gamma range.

The system and method can also be used to map secondary somatosensorycortex (SII) by focusing on late lateral responses presented in the ECoGsignals. Coherence analysis on the single trial level between the medialand the Sylvian activated locations may provide insight on the temporalrelationship between the two regions and whether the Sylvian representsa secondary processing or motor planning stage.

Little or no communication is required during the mapping. The subjectcan even be asleep during the entire mapping procedures.

The system and method disclosed herein can be implemented in real time.The cortical maps can be displayed instantaneously as vibration isdelivered to the vibrators. Physicians can evaluate the mapping anddetermine whether the mapping provides desired results so to avoidrepetition of the mapping procedures.

The system and method disclosed herein provides high-resolution corticalmapping. The resolution can be at the single-electrode level. ECoGtypically uses electrodes that are 4 mm in diameter spaced by about acentimeter. MicroECoG can use sites as small as 100 microns, spaced asclosely as 200 microns. So with the system and method disclosed herein,resolution to the level of 200 microns can be achieved. Such aresolution provides much desirable precision required by the resectionsurgery or post-surgery assessment, unlike functional magnetic resonanceimaging.

The vibrators can be placed at any location on the body. So the entiresomatosensory homunculus can be mapped with the system and method asdisclosed herein.

EXAMPLES Material and Methods

Twelve patients undergoing Phase II monitoring for epileptic focusresection at Barrow Neurological Institute at Phoenix Children'sHospital participated in this study. The scope of this paper wasrestricted to subjects (three males. four females, mean age: 11.6 years,range: 5-20 years) for whom either the clinical or the vibrotactilemapping identified finger or hand responses (see Table 1). The remainingsubjects were excluded because their ECoG grids were outside the area ofinterest (two subjects), because clinicians were unable to obtainclinical sensorimotor maps results (two subjects), or because ofincomplete recordings (1 subject).

TABLE 1 Demographics Age Tasks Wake- Surgical Gender (years) CLs ILsCLsm ILsm fulness Etiology Alleviation Sub1 M 11.8 yes yes yes yes AwakeTuberous Sclerosis Multiple resection Sub2 F 5.5 yes yes no no AwakeDevelopmental Local impairment Resection Sub3 F 8.3 yes yes no noSleeping Cortical Dysplasia Local Resection Sub4 F 8.7 yes yes no noAwake Encephalopathy None Sub5 M 10.9 yes yes yes yes Awake LennoxGastaut VNS syndrome placement Sub6 F 20.1 yes yes yes yes AwakeCortical Dysplasia Temporal Lobectomy Sub7 M 15.8 yes yes yes yes AwakePerinatal depression Occipital with Intracranial parietal hemorrhageLobectomy

All described procedures were approved by Phoenix Children's HospitalInstitutional Review Board and written informed consent was obtained bythe parents or legal guardians and/or the subjects prior to anyprocedure.

Grid locations were selected from the observations from Phase Imonitoring and no additional implants were placed for this study. Sub3was asleep during all the experimental recordings.

Patients were implanted with titanium ECoG electrode grids (10 mminter-contact distance, 4 mm diameter) and/or strips manufactured byAd-Tech Medical Instruments Corporation (Hartland, Wis.) or IntegraLifeSciences (Plainsboro, N.J.) according to clinical needs. In contrastto EEG recordings, ECoG electrodes lie on the surface of the brain,offering increased spatial resolution and higher signal to noise ratio.A Ripple Grapevine amplifier (Salt Lake City, Utah) was used to recordthe cortical signals at 500 Hz concurrently with the standard clinicalsetup (XI-Tek EMU 128). The software Bci2000 [Schalk et al., 2004]orchestrated stimulation and data acquisition. An Integra OCS2 OjemannCortical Stimulator Integra LifeSciences (Plainsboro, N.J.) was used forthe clinical mapping. Three-dimensional models of the patients' brains,grids and landmark locations were obtained using CT and MR scans. TheFreesurfer image analysis suite was used for volumetric segmentation andcortical reconstruction [Reuter et al., 2010; Rueter et al., 2012] fromMRI images. Grid extraction from CT scans and co-registration with MRscans were achieved with 3D Slicer 4.3 [Fedorov et al., 2012].Tridimensional models and analysis results were rendered using Blender2.73 (Blender Foundation). Due to postoperative swelling and theintegration of preoperative MM with postoperative CT, the recordinggrids were realigned radially to match the pial surface. Due to aninferior MRI quality on one subject, the tridimensional model with theclosest structural match was used for this subject.

Vibrotactile Stimulator

We designed a finger stimulator consisting of five 10 mm shaftlessvibration motors (Precision Microdrives) and five 0.5″ force sensitiveresistors (interlink Electronics), each encased in custom 3D-printedfinger placeholders. The individual units were placed on a slotted foampad, allowing for adjustment to the size variations in our youngpopulation, and reducing vibration interference between the fingers. Thesystem was controlled by an Arduino Pro Micro and connected to acomputer via USB, allowing bidirectional communication with therecording computer.

A custom made shield was designed to provide sufficient current to themotors and optically isolate the patients from the computer. Bci2000'ssource code was then modified to interact with the stimulator,triggering vibrations and synchronizing pressure values from the fivefingers to the cortical signals. We measured the delay as well as risingtime of the motors for correction in the data analysis.

Tasks

Subjects performed two tasks: a sensory only (s) and a sensorimotor (sm)task performed contralaterally (CL) or ipsilaterally (IL) to therecording grids of interest, leading to four experimental conditions:CLs, CLsm, ILs, and ILsm.

In the sensory only task, while patients sat comfortably in theirhospital bed, we placed their fingers on a stimulation pad designed toindividually stimulate the fingers. One hand at a time, the patients'fingers were randomly vibrated for a period ranging from 100 ms to 500ms, with an inter-stimulation interval ranging from is to 1.4 s.

In the sensorimotor task, the stimulation remained the same, but thepatients were instructed to attend to the stimulus by pressing thecorresponding finger on the recording pad. The time allowed for motorresponse was set to 54 s, with an inter-trial interval of 1.5 s. Eachset consisted of 50 trials (ten per finger), after which we switchedhands. We recorded up to 30 sets over a period of several days accordingto the patients' physical and mental status.

Data Analysis Preprocessing

Data processing and analysis were performed under Matlab 2014b (theMathWorks Inc, Natick Mass.), using the FieldTrip [Oostenveld etal.,2011] toolbox. The Bci2000 sets were imported into Matlab, baselinecorrected, and segmented into 2 seconds trial centered on stimulationonset. For sets showing significant common noise, individual channelswere re-referenced on a per-grid basis. The resulting trials were thenband-pass filtered (two-pass windowed linear-phase FIR) prior totime-only (BP: 1-30 Hz) and time-frequency analysis (BP: 1-230 Hz). Ashorter trial interval (−150 ms to 500 ms) was then used for dataanalysis to reduce boundary effects after filtering and frequencyanalysis. Time-frequency representation were calculated using a Morletwavelet transformation with multiplication in the frequency domain (20ms windows, 1 Hz precision, 7 cycles).

Background cortical recordings show a significant amount of naturalfluctuations due to variations in arousal, focus, or uncontrolledexternal stimuli during the course of the experiment, all of which couldaffect the experimental outcome. To minimize this effect, we recorded asmany trials as possible for each condition and for all statisticaltests; baseline correction was performed from 150 ms to 10 ms beforestimulation. For time series, the average value over the baseline periodwas removed from each trial. For time-frequency series, the trial powerof each frequency was divided by its baseline value, then subject to anatural logarithmic transformation, resulting in values in decibels.

Statistical Analysis

In this study, we aimed to test for a potential effect of vibrotactilestimulation and locate this effect in the time-frequency domain. Astandard way to minimize the multiple comparison problem (arising whenperforming simultaneously a large amount of statistical tests) involvesthe Bonferonni correction. This is a very conservative simultaneouslytest, and little or no sample pairs would show significant effects.

To address non-Gaussian distributions and multiple comparison issues, weused a cluster-based nonparametric permutation test described in [Marisand Oostenveld, 2007]. This test takes advantage of the fact that thereis a significant correlation between adjacenttime/frequencies/electrodes to lower the FWER, while reachingsensitivity above the Bonferonni correction.

This method results in clusters of adjacent time-space ortime-frequency-space samples with significant p-values. We used themaximum p-value of each cluster and ran 1000 Monte Carlo randompartitions to calculate significance probability. We analyzed theresponses separately, on a per-band basis, defined as Alpha (8-13 Hz),Beta (13-30 Hz), LowG 930-55 Hz), MidG (65-115 Hz) and HigG (125-230Hz).

The present invention has been described in terms of one or morepreferred embodiments, and it should be appreciated that manyequivalents, alternatives, variations, and modifications, aside fromthose expressly stated, are possible and within the scope of theinvention. The manuscript enclosed with this disclosure describesadditional background, examples, experimental data, and otherinformation, and is incorporated fully herein by reference.

1. An apparatus for mapping somatosensory and motor cortical regions ofa brain of a subject who is undergoing electrocorticoencephalographic(ECoG) recording, the apparatus comprising: a computing device; astimulation pad interconnected to said computing device, wherein saidstimulation pad is configured to be brought into physical contact with aselected region of the subject's skin; a neural interface processorinterconnected to said computing device; and an ECoG electrodes array tobe implanted on a surface of the subject's brain, wherein said ECogelectrode array is in communication with the neural interface processor.2. The apparatus of claim 1, wherein the stimulation pad comprises anenclosed space; a vibration motor disposed in said enclosed space; and aforce sensitive resistor disposed in said enclosed space.
 3. Theapparatus of claim 1, wherein the ECoG electrode is about 4 millimeter(mm) in diameter.
 4. The apparatus of claim 1, wherein the ECoGelectrode is about 100 micron in diameter.